Cardiac hypertrophy secondary to hemodynamic overload is associated with structural, contractile and electrocardiographic alterations, and in man may lead to an increased propensity for potentially lethal venticular arrhythmias. Despite the fact that these rhythm disturbances may contribute to sudden death in such patients, there have been relatively few studies of the cellular electrophysiologic consequences of hypertrophy that could increase vulnerability to arrhythmias. Previous work in this area has resulted in the demonstration and characterization of electrophysiologic changes in the hypertrophied ventricle, including lengthening of action potential duration in long-term pressure overload. The mechanism for this prolongation of repolarization is unclear and may relfect alterations in specific ionic currents. However, analysis of the effects of hypertrophy on membrane currents is complicated by the intricate anatomy of the myocardium and by electrotonic interactions with surrounding cells. Therefore, it is presently proposed that specific biochemical and enzymatic dispersion procedures to be used to obtain individual, healthy cells from the hearts of rats with experimentally-induced renal hypertension and myocardial hypertrophy. Following isolation of single myocytes from these and from control animals, intracellular microelectrodes and/or single channel recording techniques will permit a determination of their intrinsic electrophysiologic properties, regional variability and responsiveness to drugs and altered ionic environments when free of electrontonic influences. The long-term objective of this research, then, is to clarify the membrane changes occurring in cardiac cells during chronic hypertension and myocardial hypertrophy. The specific aims are: 1) to characterize myocardial electrophysiologic alterations, including regional variability, in a model of experimental chronic hypertension; 2) to determine whether electrical abnormalities and altered responses to varied ionic environments persist in single, hypertrophied myocytes; and ultimately, 3) to understand the changes occurring in specific ion channel kinetics, particularly in slow inward current (Isi) channels, during chronic hypertension and hypertrophy. This latter objective will be accomplished using new 'gigaseal' recording techniques that allow the study of currents at the level of the individual channels themselves.